SYNTHESIS, ANTIINFLAMMATORY ACTIVITY AND MOLECULAR-ORBITAL STUDIES OF A SERIES OF BENZYLIDENEAMINOXYPROPIONIC ACIDS SUBSTITUTED ON THE PHENYL RING

An examination of the antiinflammatory properties of certain beta-aminoxypropionic acids A (AOPAs) previously synthe- sized as analogs of antiinflammatory drugs with an arylacetic structure B (ArAAs), indicated that the most active acid is the (E)-3-(benzylideneaminoxy)-propionic acid (1), which was found to possess an activity comparable to that of Diclofenac (8). In an attempt to verify whether appropriate substitutions on the aromatic ring of 1 can modulate the antiinflammatory properties of this class of drugs, a series of benzylideneaminoxypropionic acids (BAOPAs) were synthesized, in which the phenyl group is substituted, in its 3 possible positions, by groups possessing different electronic, steric, and lipophilic characteristics. The antiinflammatory activity of the new compounds was determined by carrageenan-induced rat paw edema, using Diclofenac (8) as the reference drug. The pharmacological results revealed that among the BAOPAs examined, the most active are the m-chloro (7b) and p-ethoxy (7p) substituted compounds, which exhibit an antiinflammatory activity comparable to that of 1. Quantum mechanical calculations were also carried out in order to gain insight into the possible correlations between the pharmacological activity observed and the electronic and conformational effects induced by the presence of the various substituents.